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Expression of Bcl-2 Family in 4-Nitroquinoline 1-Oxide-Induced Tongue Carcinogenesis of the Rat  

Choi, Jae-Wook (Dept. of Oral Medicine, School of Dentistry, Dental Science Research Institute, Chonnam National University)
Chung, Sung-Su (Dept. of Anesthesiology, School of Dentistry, Dental Science Research Institute, Chonnam National University)
Lee, Geum-Sug (Dept. of Oral Medicine, School of Dentistry, Dental Science Research Institute, Chonnam National University)
Kim, Byung-Gook (Dept. of Oral Medicine, School of Dentistry, Dental Science Research Institute, Chonnam National University)
Kim, Jae-Hyeong (Dept. of Oral Medicine, School of Dentistry, Dental Science Research Institute, Chonnam National University)
Kook, Eun-Byul (Dept. of Oral Pathology, School of Dentistry, Dental Science Research Institute, Chonnam National University)
Jang, Mi-Sun (Dept. of Oral Pathology, School of Dentistry, Dental Science Research Institute, Chonnam National University)
Ko, Mi-Kyeong (Dept. of Oral Pathology, School of Dentistry, Dental Science Research Institute, Chonnam National University)
Jung, Kwon (Dept. of Oral Pathology, School of Dentistry, Dental Science Research Institute, Chonnam National University)
Choi, Hong-Ran (Dept. of Oral Pathology, School of Dentistry, Dental Science Research Institute, Chonnam National University)
Kim, Ok-Joon (Dept. of Oral Pathology, School of Dentistry, Dental Science Research Institute, Chonnam National University)
Publication Information
Journal of Oral Medicine and Pain / v.30, no.3, 2005 , pp. 301-317 More about this Journal
Abstract
The number of patients with tongue carcinoma is increasing rapidly among young individuals in many parts of the world. Oral carcinoma progresses from hyperplastic lesion through dysplasia to invasive carcinoma and the concept of "field cancerization" with molecular alteration has been suggested for oral cavity carcinogenesis. Significant improvement in treatment and prognosis will depend on more detailed understanding of the multi-step process leading to cancer development. To induce tongue carcinoma in rat by 4-NQO, each drinking water was made to 10 ppm, 25 ppm, 50 ppm and control (only D.W. without 4-NQO). Specimens were classified into 4 groups such as control, I (mild & moderate dysplasia), II (severe dysplasia and carcinoma in situ), III (carcinoma). The mRNA expressions of Bcl-2 family were evaluated by RT-PCR technique. For anti-apoptotic Bcl-2 family, mRNA expression of Bcl-w was down-regulated in all stages of tongue carcinogenesis model. However, mRNA expression of Bcl-2 was up-regulated. For pro-apoptotic Bcl-2 family, all members were down-regulated in all stages of tongue carcinogenesis model except for Bad mRNA in group III. In terms of BH3 only protein, mRNA expressions of Bok and Mcl-1 were down regulated in all stages of specimen, but Bmf in group II and BBC3 in group III were up-regulated. Our current findings demonstrated the involvements of mRNA expression of Bcl-2 family in multi-step tongue carcinogensis. This highlights the necessity for continued efforts to discover suitable biomakers (Bcl-2 family) for early diagnosis of the disease, and to understand its pathogenesis as a first step in improving methods of treatment. The discovery of these potential biomarkers and molecular targets for cancer diagnostics and therapeutics has the potential to significantly change the clinical approach and outcome of the disease.
Keywords
Oral cavity carcinogenesis; 4-nitroquinoline 1-oxide; mRNA expressions of Bcl-2 family; RT-PCR technique;
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1 Patridge, M., Emilion, G., Pateromichelakis, S., Phillips, E., and Langdon, J. Field cancerisation of the oral cavity: comparison of the spectrum of molecular alrerations in cases presention with both dysplastic and malignant lesions. Oral. Oncel. 1997;33: 332-337   DOI   ScienceOn
2 Shklar, G. Development of experimental oral carcinogenesis and its impact on current oral cancer research. J. Dent. Res. 1999;78: 1768-1772   DOI   PUBMED   ScienceOn
3 Eveson, J.W. Animal models of intra-oral chemical carcinogenesis: a review. J. Oral. Pathol. 1981;10: 129-146   DOI   PUBMED
4 Tanaka, T., Kawamori, T., Ohnishi, M., Okamoto, K., Mori, H. and Hara, A. Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis by dietary protocatechuic acid during initiation and postinitiation phases. Cancer Res. 1994;54: 2359-2365
5 Moore, M.A. and Tsuda, H. Chronically elevated proliferation as a risk factor for neoplasia. Eur. J. Cancer Prev. 1998;7: 353-385   DOI   ScienceOn
6 Ziwei, H. Bcl-2 proteins as target for anticancer durg design. Oncogene. 2000;19: 6627-6631   DOI   PUBMED   ScienceOn
7 Lam, M., Dubyak, G., Chen, L., Nunez, G., Miesfeld, R.L., Distelhorst, C.W.. Evidence that BCL-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca2+ fluxes. Proc Natl Acad Sci U S A. 1994;91: 6569-6573
8 Nakano, K., Vousden,K.H. PUMA, a novel proapoptotic gene, is induced by p53. Mol. Cell. 2001; 7: 683-694   DOI   ScienceOn
9 Jordan RC, Catzavelos GC, Barrett AW, Speight PM. Differential expression of bcl-2 and bax in squamous cell carcinomas of the oral cavity. Eur J Cancer B Oral Oncol. 1996;32(6):394-400   DOI   ScienceOn
10 Krajewski S, Krajewska M, Shabaik A, Miyashita T, Wang HG, Reed JC. Immunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2. Am J Pathol. 1994 ;145(6):1323-36
11 Li D, Ueta E, Kimura T, Yamamoto T, Osaki T. Reactive oxygen species (ROS) control the expression of Bcl-2 family proteins by regulating their phosphorylation and ubiquitination. Cancer Sci. 2004;95(8):644-50   DOI   ScienceOn
12 Masuda M, Suzui M, Lim JT, Weinstein IB Epigallocatechin-3-gallate inhibits activation of HER-2/neu and downstream signaling pathways in human head and neck and breast carcinoma cells. Clin Cancer Res. 2003;9(9):3486-91
13 Mihara M, Shintani S, Kiyota A, Matsumura T, Wong DT. Cyclin-dependent kinase inhibitor (roscovitine) suppresses growth and induces apoptosis by regulating Bcl-x in head and neck squamous cell carcinoma cells. Int J Oncol. 2002 ;21(1):95-101
14 Huang DC, Strasser A. BH3-Only proteins-essential initiators of apoptotic cell death. Cell. 2000;103(6):839-42   DOI   ScienceOn
15 Ohne, M., Satoh, T., Yamada, S. and Takai, H. Experimental tongue carcinoma of rats induced by oral administration of 4-nitroquinoline 1-oxide (4-NQO) in drinking water. Oral Surg. Oral Med. Oral Pathol. 1985;59: 600-607   DOI   ScienceOn
16 Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol 1980;68: 251-306   DOI   PUBMED
17 M. Krajewska, S.F. Moss, S. Krajewski, K Song, P.R. Holt and J.C. Reed, Elevated expression of Bcl-X and reduced Bak in primary colorectal adenocarcinomas. Cancer Research 1996; 56(10) : 2422–2427
18 Mikhailov, V., Mikhailova, M., Pulkrabek, D.J., Dong, Z., Venkatachalam, M.A., Saikumar, P. Bcl-2 prevents Bax oligomerization in the mitochondrial outer membrane. J Biol Chem. 2001;276:18361-18374   DOI   ScienceOn
19 Akao, Y., Otsuki, Y., Kataoka, S., Ito, Y., Tsujimoto, Y. Multiple subcellular localization of bcl-2: detection in nuclear outer membrane, endoplasmic reticulum membrane, and mitochondrial membranes. Cancer Res. 1994;54: 2468-2471
20 Koide N, Koike S, Adachi W, Amano J, Usuda N, Nagata T. Immunohistochemical expression of bcl-2 protein in squamous cell carcinoma and basaloid carcinoma of the esophagus. Surg Today. 1997;27(8):685-91   DOI   ScienceOn
21 Pinton, P., Ferrari, D., Magalhaes, P., et al. Reduced loading of intracellular Ca(2+) stores and downregulation of capacitative Ca(2+) influx in Bcl-2-overexpressing cells. J Cell Biol. 2000;148: 857-862   DOI   ScienceOn
22 Murphy, K.M., Streips, U.N., Lock, R.B. Bcl-2 inhibits a Fas-induced conformational change in the Bax N terminus and Bax mitochondrial translocation. J Biol Chem. 2000;275:17225-17228   DOI   ScienceOn
23 O'Reilly L. A., Print C., Hausmann G., et al. Tissue expression and subcellular localization of the pro-survival molecule Bcl-w. Cell Death Differ., 2001;8:486-494   DOI   ScienceOn
24 M.C. Kiefer, M.J. Brauer, V.C. Powers et al., Modulation of apoptosis by the widely distributed Bcl-2 homologue Bak. Nature 2002 ;374: 736 - 739   DOI   ScienceOn
25 Reed, J.C., Miyashita, T., Takayama, S., et al. BCL-2 family proteins: regulators of cell death involved in the pathogenesis of cancer and resistance to therapy.J Cell Biol. 1996;60: 23-32
26 Hsu, S.Y., Hsueh, A.J. A splicing variant of the Bcl-2 member Bok with a truncated BH3 domain induces apoptosis but does not dimerize with antiapoptotic Bcl-2 proteins in vitro. J Biol Chem. 1998;273: 30139-30146   DOI   PUBMED
27 Nakopoulou L, Vourlakou C, Zervas A, Tzonou A, Gakiopoulou H, Dimopoulos MA. The prevalence of bcl-2, p53, and Ki-67 immunoreactivity in transitional cell bladder carcinomas and their clinicopathologic correlates. Hum Pathol. 1998;29(2):146-54   DOI   ScienceOn
28 Antonsson, B., Montessuit, S., Lauper, S., Eskes, R., Martinou, J.C. Bax oligomerization is required for channel-forming activity in liposomes and to trigger cytochrome c release from mitochondria. Biochem J. 2000 ;345 Pt 2: 271-278   DOI   ScienceOn
29 Jurgensmeier, J.M., Xie, Z., Deveraux, Q., Ellerby, L., Bredesen, D., Reed, J.C. Bax directly induces release of cytochrome c from isolated mitochondria.Proc Natl Acad Sci U S A. 1998;95: 4997-5002
30 Oltvai, Z.N., Korsmeyer, S.J. Checkpoints of dueling dimers foil death wishes. Cell. 1994 ;79: 189-92   DOI   ScienceOn
31 Oltvai, Z.N., Milliman, C.L., Korsmeyer, S.J. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993 ;74: 609-19   DOI   PUBMED   ScienceOn
32 Foyouzi-Youssefi, R., Arnaudeau, S., Borner, C., et al. Bcl-2 decreases the free Ca2+ concentration within the endoplasmic reticulum. Proc Natl Acad Sci U S A. 2000;97: 5723-5728
33 Calfano, J., van der Riet, P., Westra, W., Nawroz, H., Clayman,G., Piantadosi, S., Corio, R., Lee, D., Greenberg, B., Koch, W. and Sidransky, D. Genetic progression model for head and neck cancer: implications for field cancerization. Cancer Res. 1996;56: 2488-2492
34 He, H., Lam, M., McCormick, T.S., Distelhorst, C.W. Maintenance of calcium homeostasis in the endoplasmic reticulum by Bcl-2. J Cell Biol. 1997;138: 1219-28   DOI   ScienceOn
35 Chrysomali E, Greenspan JS, Dekker N, Greenspan D, Regezi JA. Apoptosis-associated proteins in oral hairy leukoplakia. Oral Dis. 1996 ;2(4):279-84   DOI   ScienceOn
36 Mori, H., Sugie, S., Yoshimi, N., Hara, A. and Tanaka, T. control of cell proliferation in cancer prevention. Mutat Res. 1999;428: 291-298   DOI
37 Nakano K, Vousden KH. PUMA, a novel porapoptotic gene, is induced by p53. Molecular Cell 2001;7: 683-694   DOI   ScienceOn
38 Han J, Flemington C, Houghton AB, et al. Expression of bbc3, a pro-apoptotoic Bch3-only gene, is regulated by diverse cell death and survival signals. Proceedings of the National Academy of Sciences of the USA. 2001;98:11318-11323
39 Slaughter, D.L., Southwick, H.W., Smejkal, W. Filed cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer. 1953;6: 963-968   DOI   PUBMED   ScienceOn
40 Sharma, R.A., Manson, M.M., Gescher, A. and Steward, W.P. Colorectal cancer chemoprevention: biochemical targets and clinical development of promising agents. Eur. J. Cancer. 2001;37: 12-22
41 Lee HW, Lee SS, Lee SJ, Um HD. Bcl-w is expressed in a majority of infiltrative gastric adenocarcinomas and suppresses the cancer cell death by blocking stress-activated protein kinase/c-Jun NH2-terminal kinase activation. Cancer Res. 2003;63(5):1093-100
42 S. Krajewski, M. Krajewska and J.C. Reed, Immunohistochemical analysis of in vivo patterns of Bak expression, a proapoptotic member of the Bcl-2 protein family. Cancer Research 1996; 56(12): 2849-2855
43 Steidler, N.E., and Reade, P.C. Initiation and promotion of experimental oral mucosal carcinogenesis in mice. J. Oral. Pathol. 1986;15: 43-47   DOI   PUBMED
44 Reed, J.C. Bcl-2 and the regulation of programmed cell death. J Cell Biol. 1994;124: 1-6   DOI   ScienceOn
45 John, CR. Bcl-2 family proteins. Oncogene. 1998;17: 3225-3236   DOI   PUBMED   ScienceOn
46 Wilson JW, Nostro MC, Balzi M, et al. Bcl-w expression in colorectal adenocarcinoma. Br J Cancer. 2000;82(1):178-85   DOI   ScienceOn
47 Ravi D, Nalinakumari KR, Rajaram RS, Nair MK, Pillai MR. Expression of programmed cell death regulatory p53 and bcl-2 proteins in oral lesions. Cancer Lett. 1996;105(2):139-46   DOI   ScienceOn
48 Loro LL, Vintermyr OK, Liavaag PG, Jonsson R, Johnnessen AC. Oral squamous cell carcinoma is associated with decreased bcl-2/bax expression ratio and incresed apoptosis. Hum Pathol ;30:1097-1105   DOI   ScienceOn
49 Itoh M, Noutomi T, Chiba H, Mizuguchi J. BcI-xL antisense treatment sensitizes Bcl-xL-overexpressing squamous cell carcinoma cells to carboplatin. Oral Oncol. 2002 ;38(8):752-6   DOI   ScienceOn
50 Fisker, A.V. Experimental oral carcinogenesis. A basic rat model for the study of oral carcinogenesis using the carcinogen 4-nitroquinoline 1-oxide. Dan. Med. Bull. 1990;15:43-47
51 Xie X, Clausen OP, Boysen M. Prognostic value of Bak expression in oral tongue squamous cell carcinomas. Oncol Rep. 2003 ;10(2):369-74
52 Wei, M.C., Zong, W.X., Cheng, E.H., Lindsten, T., Panoutsakopoulou, V., Ross, A.J., Roth, K.A., Macgregor, G.R., Thompson, C.B., and Korsmeyer, S.J. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science. 1998;292: 727-730
53 Show, M.D., Folmer, J.S., Anway, M.D., Zirkin, B.R. Testicular expression and distribution of the rat bcl2 modifying factor in response to reduced intratesticular testosterone. Biol Reprod. 2004;70: 1153-1161   DOI   ScienceOn
54 Wallenius, K. and Lekholm, U. Oral cancer in rats induced by the water soluble carcinogen 4-nitroquinoline 1-oxide. Odont. Rev. 1973;24: 39-48
55 Adams, J.M., Cory, S. The Bcl-2 protein family: arbiters of cell survival. Science. 1998;281: 1322-1326   DOI   PUBMED   ScienceOn
56 Wei, M.C., Lindsten, T., Mootha, V.K., et al. tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. Genes Dev. 2000;14: 2060-71
57 Nutt, L.K., Pataer, A., Pahler, J., et al. Bax and Bak promote apoptosis by modulating endoplasmic reticular and mitochondrial Ca2+ stores. J Biol Chem. 2002;277: 9219-9225   DOI   ScienceOn
58 Okazaki Y, Tanaka Y, Tonogi M, Yamane G. Ivestigation of environmental factors for diagnosting malignant potential in oral epithelial dysplasia
59 Zong, W.X.,, Lindsten, T., Ross, A.J., MacGregor. G.R., Thompson, C.B. BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak. Genes Dev. 2001;15: 1481-1486   DOI   ScienceOn
60 M. Krajewska, C.M. Fenoglio-Preiser, S. Krajewski et al., Immunohistochemical analysis of Bcl-2 family proteins in adenocarcinomas of the stomach. American Journal of Pathology 1996; 149(5): 1449-1457
61 Ferrer A, Marce S, Bellosillo B, et al. Activation of mitochondrial apoptotic pathway in mantle cell lymphoma: high sensitivity to mitoxantrone in cases with functional DNA-damage response genes. Oncogene. 2004; 23(55) : 8941-9.   DOI   ScienceOn
62 Reed JC. Mechanisms of apoptosis avoidance in cacner. Curr Opin Oncol 1999; 11:68-75   DOI   PUBMED   ScienceOn
63 Yu, J., Zhang, L., Hwang, P.M., Kinzler, K.W., Vogelstein, B. PUMA induces the rapid apoptosis of colorectal cancer cells. Mol. Cell. 2001;7: 673-682   DOI   ScienceOn